Is DYNAP p.Cys65Phe (c.194G>T) pathogenic?

DYNAP p.Cys65Phe (c.194G>T) is classified Uncertain significance in DYNAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-27). AlphaMissense: likely benign (0.101); Very rare (popmax 0.0088%, sas).

How common is DYNAP p.Cys65Phe (c.194G>T) in the general population?

DYNAP p.Cys65Phe (c.194G>T) is very rare (popmax 0.0088%, sas) (gnomAD).

What do computational predictors say about DYNAP p.Cys65Phe (c.194G>T)?

AlphaMissense predicts likely benign (score 0.101) — an in-silico prediction, not a clinical call.

DYNAP p.Cys65Phe

c.194G>T · VCV4015545

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.101 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0088%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.101	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -6.41	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.18	GERP -1.6
Regional constraint	o/e 1.14	unconstrained · MANE · 6,859 bp · p 0.034 · regional, not allelic
Overall
CADD	0.922	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM C91F vs ClinVar C65F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0088% South Asian · 8/90,910 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00313%

Overall 0.00062% 10/1,612,250 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0088%	11,364
East Asian	0.00223%	44,836
Remaining individualsnot grpmax-eligible	0.0016%	62,412

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: DYNAP
Protein: p.Cys65Phe
Coding: c.194G>T
MANE Select: NM_173629
Type: single nucleotide variant
Location: chr18:54595075 (GRCh38)
Gene constraint: LOEUF 1.221 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 60.24

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

Similar variants

DYNAP c.13A>C Uncertain significance ★ ⚠ same type
DYNAP c.14T>C Uncertain significance ★ same type
DYNAP c.20G>A Uncertain significance ★ ⚠ same type
DYNAP c.28C>A Uncertain significance ★ ⚠ same type
DYNAP c.-29G>C Uncertain significance ★ ⚠ same type
DYNAP p.Ala158Asp Uncertain significance ★ ⚠ same type
DYNAP p.Ala169Thr Uncertain significance ★ ⚠ same type
DYNAP p.Ala29Pro 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/dynap-p-cys65phe (accessed [today's date]).

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