Is PTCD3 p.Ala2Val (c.5C>T) pathogenic?

PTCD3 p.Ala2Val (c.5C>T) is classified Benign in PTCD3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-05-22). AlphaMissense: ambiguous (0.5319); Common (popmax 13.9%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about PTCD3 p.Ala2Val (c.5C>T)?

AlphaMissense predicts ambiguous (score 0.5319) — an in-silico prediction, not a clinical call.

PTCD3 p.Ala2Val

Q: How common is PTCD3 p.Ala2Val (c.5C>T) in the general population?

PTCD3 p.Ala2Val (c.5C>T) is common (popmax 13.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.5C>T · rs13393659 · VCV1273760

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.5319 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 13.9%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.5319	ambiguous
REVEL	0.156	moderately benign-leaning
SaProt	LLR -9.35	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.7	GERP 1.9, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 31 kb · p 0.15 · regional, not allelic
Overall
CADD	24.4	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 13.9% African / African-American · 10,425/74,974 alleles

Filtering AF 13.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 13.6%

Overall 0.751% 12,120/1,613,754 alleles · common exomes 6,075/1,461,470 · genomes 6,045/152,284 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	13.9%	7
Admixed American	0.963%	104
Remaining individualsnot grpmax-eligible	0.938%	107
Middle Eastern	0.76%	132
South Asian	0.0538%	1,857
European (non-Finnish)	0.0368%	2,718
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,598
East Asian	0.00223%	44,872

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: PTCD3
Protein: p.Ala2Val
Coding: c.5C>T
MANE Select: NM_017952
dbSNP: rs13393659
Type: single nucleotide variant
Location: chr2:86106252 (GRCh38)

Full PTCD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/ptcd3-p-ala2val (accessed [today's date]).

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