Is DRD4 p.Ala77Val (c.230C>T) pathogenic?

DRD4 p.Ala77Val (c.230C>T) is classified Uncertain significance in DRD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-27). AlphaMissense: likely pathogenic (0.9321); Very rare (popmax 0.0063%, nfe).

How common is DRD4 p.Ala77Val (c.230C>T) in the general population?

DRD4 p.Ala77Val (c.230C>T) is very rare (popmax 0.0063%, nfe) (gnomAD).

What do computational predictors say about DRD4 p.Ala77Val (c.230C>T)?

AlphaMissense predicts likely pathogenic (score 0.9321) — an in-silico prediction, not a clinical call.

DRD4 p.Ala77Val

c.230C>T · VCV3505235

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9321 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0063%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9321	likely pathogenic
REVEL	0.381	indeterminate
SaProt	LLR -14.23	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP 2.2, phastCons 1
Regional constraint	o/e 1.44	unconstrained · MANE · 3,295 bp · p 6.5e-29 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0063% European (non-Finnish) · 73/1,159,552 alleles

Filtering AF 0.00512% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00471%

Overall 0.00556% 87/1,563,648 alleles · very rare exomes 81/1,411,468 · genomes 6/152,180 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0063%	15,884
Admixed American	0.00561%	17,839
East Asian	0.00471%	21,241
South Asian	0.00468%	21,377
Ashkenazi Jewishnot grpmax-eligible	0.00347%	28,854
Remaining individualsnot grpmax-eligible	0.00329%	30,421
African / African-American	0.0027%	37,057

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: DRD4
Protein: p.Ala77Val
Coding: c.230C>T
MANE Select: NM_000797
Type: single nucleotide variant
Location: chr11:637534 (GRCh38)
Gene constraint: LOEUF 1.952 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.06 · 2 PDB
Residue 77: an α-helix

Full DRD4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DRD4 p.Asn309Asp Uncertain significance ★★ ⚠ same type
DRD4 p.Ser308Pro Uncertain significance ★★ ⚠ same type
DRD4 p.Ala335Gly Benign ★★ same type
DRD4 p.Gly11Arg Benign ★★ same type
DRD4 p.Leu83= Likely benign ★★ same type
DRD4 p.Pro244= Likely benign ★★ same type
DRD4 p.Pro248= Likely benign ★★ same type
DRD4 p.Val398= Likely benign ★★ 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/drd4-p-ala77val (accessed [today's date]).

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