Is CLVS1 p.Thr34Ala (c.100A>G) pathogenic?

CLVS1 p.Thr34Ala (c.100A>G) is classified Uncertain significance in CLVS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-13). AlphaMissense: likely benign (0.1235); Very rare (popmax 0.00334%, amr).

How common is CLVS1 p.Thr34Ala (c.100A>G) in the general population?

CLVS1 p.Thr34Ala (c.100A>G) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about CLVS1 p.Thr34Ala (c.100A>G)?

AlphaMissense predicts likely benign (score 0.1235) — an in-silico prediction, not a clinical call.

CLVS1 p.Thr34Ala

c.100A>G · VCV3267944

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1235 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1235	likely benign
REVEL	0.641	indeterminate
SaProt	LLR -7.52	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 190 bp · p 0.23 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00334% Admixed American · 2/59,962 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.00031% 5/1,613,902 alleles · very rare exomes 4/1,461,694 · genomes 1/152,208 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,981
South Asian	0.0022%	45,542
European (non-Finnish)	8.47e-05%	1,179,942

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.Thr34Ala
Coding: c.100A>G
MANE Select: NM_173519
Type: single nucleotide variant
Location: chr8:61299927 (GRCh38)
Gene constraint: LOEUF 0.473 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 82.01

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-thr34ala (accessed [today's date]).

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