Is CDIPT p.Met77Val (c.229A>G) pathogenic?

CDIPT p.Met77Val (c.229A>G) is classified Uncertain significance in CDIPT (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-13). AlphaMissense: ambiguous (0.3634); Ultra-rare (popmax 0.0791%, sas).

How common is CDIPT p.Met77Val (c.229A>G) in the general population?

CDIPT p.Met77Val (c.229A>G) is ultra-rare (popmax 0.0791%, sas) (gnomAD).

What do computational predictors say about CDIPT p.Met77Val (c.229A>G)?

AlphaMissense predicts ambiguous (score 0.3634) — an in-silico prediction, not a clinical call.

CDIPT p.Met77Val

c.229A>G · rs766385869 · VCV2368686

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3634 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0791%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3634	ambiguous
REVEL	0.239	benign-leaning
SaProt	LLR -6.84	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 3,665 bp · p 0.068 · regional, not allelic
Overall
CADD	23.4	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 0.0791% South Asian · 72/91,080 alleles

Filtering AF 0.0643% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0589%

Overall 0.00967% 156/1,613,990 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0791%	1,265
Admixed American	0.015%	6,666
Remaining individualsnot grpmax-eligible	0.0064%	15,622
European (non-Finnish)	0.00593%	16,857
African / African-American	0.00133%	74,916

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: CDIPT
Protein: p.Met77Val
Coding: c.229A>G
MANE Select: NM_006319
dbSNP: rs766385869
Type: single nucleotide variant
Location: chr16:29861209 (GRCh38)
Gene constraint: LOEUF 1.042 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.02

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

Similar variants

CDIPT p.Ala140Ser Uncertain significance ★ ⚠ same type
CDIPT p.Ala146Ser Uncertain significance ★ ⚠ same type
CDIPT p.Ala206Val Uncertain significance ★ ⚠ same type
CDIPT p.Ala22Ser Uncertain significance ★ ⚠ same type
CDIPT p.Ala48Thr Uncertain significance ★ same type
CDIPT p.Ala84Val Uncertain significance ★ ⚠ same type
CDIPT p.Arg115Gln Uncertain significance ★ ⚠ same type
CDIPT p.Arg138Lys 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/cdipt-p-met77val (accessed [today's date]).

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