Is AVPR1B p.Phe424Ser (c.1271T>C) pathogenic?

AVPR1B p.Phe424Ser (c.1271T>C) is classified Uncertain significance in AVPR1B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-17). AlphaMissense: likely benign (0.1201); Very rare (popmax 0.00134%, afr).

How common is AVPR1B p.Phe424Ser (c.1271T>C) in the general population?

AVPR1B p.Phe424Ser (c.1271T>C) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about AVPR1B p.Phe424Ser (c.1271T>C)?

AlphaMissense predicts likely benign (score 0.1201) — an in-silico prediction, not a clinical call.

AVPR1B p.Phe424Ser

c.1271T>C · rs902316568 · VCV3132434

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1201 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.1201	likely benign
SaProt	LLR -5.35	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.1, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 6,698 bp · p 0.11 · regional, not allelic
Overall
CADD	18.42	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 0.00134% African / African-American · 1/74,620 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.00025% 4/1,602,796 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,620
European (non-Finnish)	0.000256%	390,628

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: AVPR1B
Protein: p.Phe424Ser
Coding: c.1271T>C
MANE Select: NM_000707
dbSNP: rs902316568
Type: single nucleotide variant
Location: chr1:206110193 (GRCh38)
Gene constraint: LOEUF 1.194 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.18

Full AVPR1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AVPR1B p.Leu113Val Uncertain significance ★★ ⚠ same type
AVPR1B p.Thr129= Likely benign ★★ same type
AVPR1B p.Trp187Arg Likely benign ★★ same type
AVPR1B p.Ala319Thr Uncertain significance ★ ⚠ same type
AVPR1B p.Ala34Thr Uncertain significance ★ ⚠ same type
AVPR1B p.Arg132Cys Uncertain significance ★ ⚠ same type
AVPR1B p.Arg141His Uncertain significance ★ ⚠ same type
AVPR1B p.Arg175Trp 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/avpr1b-p-phe424ser (accessed [today's date]).

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