Is RFC2 p.Ala232Val (c.695C>T) pathogenic?

RFC2 p.Ala232Val (c.695C>T) is classified Likely benign in RFC2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-05-01). AlphaMissense: likely pathogenic (0.7764); Rare (popmax 0.691%, sas).

How common is RFC2 p.Ala232Val (c.695C>T) in the general population?

RFC2 p.Ala232Val (c.695C>T) is rare (popmax 0.691%, sas) (gnomAD).

What do computational predictors say about RFC2 p.Ala232Val (c.695C>T)?

AlphaMissense predicts likely pathogenic (score 0.7764) — an in-silico prediction, not a clinical call.

RFC2 p.Ala232Val

c.695C>T · rs3135684 · VCV723095

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.7764 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.691%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7764	likely pathogenic
REVEL	0.403	indeterminate
SaProt	LLR -12.29	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 9.9	GERP 6.2, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 22 kb · p 0.012 · regional, not allelic
Overall
CADD	28.7	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 0.691% South Asian · 629/91,062 alleles

Filtering AF 0.646% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.628%

Overall 0.132% 2,130/1,612,926 alleles · rare exomes 1,980/1,460,700 · genomes 150/152,226 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.691%	145
Ashkenazi Jewishnot grpmax-eligible	0.351%	285
Middle Eastern	0.248%	404
Remaining individualsnot grpmax-eligible	0.154%	651
Admixed American	0.138%	723
European (non-Finnish)	0.0997%	1,003
African / African-American	0.0293%	3,409
Finnishnot grpmax-eligible	0.00469%	21,339
East Asian	0.00446%	22,430

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: RFC2
Protein: p.Ala232Val
Coding: c.695C>T
MANE Select: NM_181471
dbSNP: rs3135684
Type: single nucleotide variant
Location: chr7:74238987 (GRCh38)
Gene constraint: LOEUF 1.394 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.63 · 16 PDB
Residue 232: an α-helix; a UniProt-annotated variant site (in)

Full RFC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RFC2 p.Ala232= Likely benign ★ same residue
RFC2 p.Ala196Thr Uncertain significance ★★ ⚠ same type
RFC2 c.759+8C>T Benign ★★ same type
RFC2 p.Arg201= Benign ★★ same type
RFC2 p.His33= Benign ★★ same type
RFC2 p.Thr129= Benign ★★ same type
RFC2 p.Ala150Val Uncertain significance ★ ⚠ same type
RFC2 p.Ala15Val 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/rfc2-p-ala232val (accessed [today's date]).

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