Is PVALB p.Ala41Val (c.122C>T) pathogenic?

PVALB p.Ala41Val (c.122C>T) is classified Benign in PVALB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-26). AlphaMissense: likely benign (0.1018); Low-frequency (popmax 3.93%, afr).

How common is PVALB p.Ala41Val (c.122C>T) in the general population?

PVALB p.Ala41Val (c.122C>T) is low-frequency (popmax 3.93%, afr) (gnomAD).

What do computational predictors say about PVALB p.Ala41Val (c.122C>T)?

AlphaMissense predicts likely benign (score 0.1018) — an in-silico prediction, not a clinical call.

PVALB p.Ala41Val

c.122C>T · rs74804322 · VCV781616

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1018 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.93%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1018	likely benign
REVEL	0.151	moderately benign-leaning
SaProt	LLR -8.81	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 1	GERP -0.6
Overall
CADD	17.57	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 3.93% African / African-American · 2,951/75,008 alleles

Filtering AF 3.82% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.77%

Overall 0.202% 3,257/1,614,110 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.93%	25
Remaining individualsnot grpmax-eligible	0.216%	463
Admixed American	0.205%	488
Middle Eastern	0.0825%	1,212
European (non-Finnish)	0.00331%	30,256
South Asian	0.00329%	30,360
East Asian	0.00223%	44,878

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: PVALB
Protein: p.Ala41Val
Coding: c.122C>T
MANE Select: NM_005368 · reported on NM_001315532
dbSNP: rs74804322
Type: single nucleotide variant
Location: chr22:36815175 (GRCh38)
Structure: AlphaFold pLDDT 97.26 · 1 PDB
Residue 41: an α-helix; the globin domain

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

Similar variants

MB p.His98Tyr Pathogenic/Likely pathogenic ★★ same type
MB p.Leu150Pro Uncertain significance ★★ ⚠ same type
PVALB p.Gly65Arg Benign ★★ same type
MB p.Ala72Thr Uncertain significance ★ ⚠ same type
MB p.Ala95Val Uncertain significance ★ ⚠ same type
MB p.Arg140Trp Uncertain significance ★ ⚠ same type
MB p.Asp142Gly Uncertain significance ★ same type
MB p.Glu149Asp 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/pvalb-p-ala41val (accessed [today's date]).

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