Is CLVS1 p.Glu171Lys (c.511G>A) pathogenic?

CLVS1 p.Glu171Lys (c.511G>A) is classified Uncertain significance in CLVS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-11). AlphaMissense: likely pathogenic (0.5961); Very rare (popmax 0.00666%, amr).

How common is CLVS1 p.Glu171Lys (c.511G>A) in the general population?

CLVS1 p.Glu171Lys (c.511G>A) is very rare (popmax 0.00666%, amr) (gnomAD).

What do computational predictors say about CLVS1 p.Glu171Lys (c.511G>A)?

AlphaMissense predicts likely pathogenic (score 0.5961) — an in-silico prediction, not a clinical call.

CLVS1 p.Glu171Lys

c.511G>A · rs143211270 · VCV4230396

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5961 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00666%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.5961	likely pathogenic
REVEL	0.425	indeterminate
SaProt	LLR -7.33	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 158 kb · p 5.9e-07 · regional, not allelic
Overall
CADD	27.5	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 0.00666% Admixed American · 4/60,018 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000805% 13/1,614,094 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00666%	15,004
South Asian	0.00439%	22,767
Remaining individualsnot grpmax-eligible	0.0016%	62,504
African / African-American	0.00133%	75,044
European (non-Finnish)	0.000254%	393,328

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: CLVS1
Protein: p.Glu171Lys
Coding: c.511G>A
MANE Select: NM_173519
dbSNP: rs143211270
Type: single nucleotide variant
Location: chr8:61376660 (GRCh38)
Gene constraint: LOEUF 0.473 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 82.01
Residue 171: the cral-trio domain

Full CLVS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLVS1 p.Ala28Ser Uncertain significance ★ ⚠ same type
CLVS1 p.Arg39Cys Uncertain significance ★ ⚠ same type
CLVS1 p.Asn153Asp Uncertain significance ★ ⚠ same type
CLVS1 p.Asn178Ser Uncertain significance ★ ⚠ same type
CLVS1 p.Asn224Ser Uncertain significance ★ ⚠ same type
CLVS1 p.Asn346Thr Uncertain significance ★ ⚠ same type
CLVS1 p.Asp106Asn Uncertain significance ★ ⚠ same type
CLVS1 p.Asp114Asn Uncertain significance ★ ⚠ same type

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/clvs1-p-glu171lys (accessed [today's date]).

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