Is COMP p.Ala171Thr (c.511G>A) pathogenic?

COMP p.Ala171Thr (c.511G>A) is classified Benign/Likely benign in COMP (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-05-13). AlphaMissense: likely pathogenic (0.7279); Common (popmax 5.81%, afr) — too common for a highly-penetrant pathogenic allele; Associated with connective tissue disorder.

What condition is associated with COMP p.Ala171Thr (c.511G>A)?

COMP p.Ala171Thr (c.511G>A) is associated with connective tissue disorder, multiple epiphyseal dysplasia type 1, pseudoachondroplasia (ClinVar).

What do computational predictors say about COMP p.Ala171Thr (c.511G>A)?

AlphaMissense predicts likely pathogenic (score 0.7279) — an in-silico prediction, not a clinical call.

COMP p.Ala171Thr

Q: How common is COMP p.Ala171Thr (c.511G>A) in the general population?

COMP p.Ala171Thr (c.511G>A) is common (popmax 5.81%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.511G>A · rs115338183 · VCV197627

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

AlphaMissense

likely pathogenic

0.7279 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 5.81%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

connective tissue disorder

Computational evidence

Protein change
AlphaMissense	0.7279	likely pathogenic
REVEL	0.603	indeterminate
SaProt	LLR -12.85	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 2, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 8,351 bp · p 2.2e-07 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.81% African / African-American · 4,254/73,196 alleles

Filtering AF 5.67% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.61%

Overall 0.309% 4,885/1,579,168 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.81%	17
Middle Eastern	0.477%	209
Admixed American	0.473%	211
Remaining individualsnot grpmax-eligible	0.387%	258
European (non-Finnish)	0.00951%	10,516
South Asian	0.00937%	10,675
East Asian	0.00226%	44,296

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: COMP
Protein: p.Ala171Thr
Coding: c.511G>A
MANE Select: NM_000095
dbSNP: rs115338183
Type: single nucleotide variant
Location: chr19:18789177 (GRCh38)
Gene constraint: LOEUF 1.073 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.60 · 1 PDB
Residue 171: the egf-like 2; calcium-binding domain; a disulfide bond

Full COMP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

connective tissue disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: multiple epiphyseal dysplasia type 1 pseudoachondroplasia carpal tunnel syndrome 2

Similar variants

COMP p.Arg718Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
COMP p.Asn489Lys Pathogenic/Likely pathogenic ★★ same condition
COMP p.Asn523Lys Pathogenic/Likely pathogenic ★★ same condition
COMP p.Asn555Lys Pathogenic/Likely pathogenic ★★ same condition
COMP p.Asp269Gly Pathogenic/Likely pathogenic ★★ same condition
COMP p.Asp273Val Likely pathogenic ★★ same condition
COMP p.Asp326Asn Pathogenic/Likely pathogenic ★★ same condition
COMP p.Asp349His Pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/comp-p-ala171thr (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown